Asymmetric reactions regioselectivity

An important consideration in designing and performing asymmetric reactions with high regioselectivity and enantioselectivity, especially for those in which more than one stereogenic center is formed, is the need to carry out the reaction with a combination of kinetic resolution in the initial asymmetric synthesis. 

Do not suppose that the regioselectivity problem is now trivial. In a study mainly aimed at achieving asymmetric reactions, Braun34 showed just how narrow is the gap between 1,2 and 1,4 addition. The silyl enol ether 101, easily made from the enantiomerically pure ester 100, gave mainly (>95 5) direct (1,2) addition to a simple enone under the usual conditions (TiCl4 catalysis) for Michael addition. 

Non-crosslinked polystyrene with salen ligand Non-crosslinked polystyrene with onium salt residues Non-crosslinked polystyrene copolymerised with a chiral phosphine ligand 14,765 0.5-3.8" 0.7-2.3 CH2Cl2,THF, EtOAc, DMF DMF,DMSO,DMA, toluene, anisole, MeOH,MeCN, diglyme Asymmetric epoxidation Regioselective addition reaction of phenyl glycidyl ether with S-phenyl thioacetate Pt-catalysed asymmetric hydroformylation of olefins Precipitation (methanol) (r) Precipitation (diethyl ether) (r) [68] [142] [143]... 

Review. These products have become of special interest since they are now available in optically pure form by asymmetric dihydroxylation of alkenes. In addition, the regioselectivity in reactions with nucleophiles can differ from that of epoxides and the yields can be superior. The reference covers literature from 1863 through 1991 (104 references). 

Pericyclic Reactions. Trimethylsilyldiazomethane reacts with chiral acrylates to create optically active A -pyrazolines via regioselective asymmetric [3+2] cycloaddition. Subsequent pro-todesilylation affords A -pyrazolines in good yields (eq 66). This procedure offers a convenient route to azaprolines. ... 

Various reactions of pronucleophiles with allenes has been reviewed by Yamamoto and Radhakrishnan [18]. Regioselectivity in these reactions is controlled by steric and electronic effects. The attack at C-3 is a main path, but several exceptional cases have been reported. Due to electronic bias, the hydrocarbonation of alkoxy- or phenoxyallenes 70 gives allylic ethers as the C-1 adduct 72 either exclusively or predominantly via 7r-allylpalladium 71 [19]. Trost expanded the regioselective formation of allylic ether to an asymmetric reaction. Addition of the Meldrum s acid 74 to the allenyl ether 73 catalyzed by palladium trifluoroacetate and (5, 5)-XIII-l as a chiral ligand in the presence of trifluoroacetic acid afforded the the allylic ether 75 with 99 % ee in 75 % yield [20]. 

Another interesting apphcation of palladium catalyzed aUcoxycarbonylation has been the highly regioselective intramolecular reaction of a variety of 2-allylphenols to generate five- to seven-membered ring lactones (Scheme 14.31). Asymmetric variants would be of interest. 

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